The compounds of general formula-1 and its use in the preparation of rosuvastatin was first disclosed in WO 2008/44243. The disclosed process involves the condensation of N-(4-(4-fluorophenyl)-6-isopropyl-5-((1-methyl-1H-benzo[d]imidazol-2-ylsulfonyl) methyl)pyrimidin-2-yl)-N-methylmethanesulfonamide with N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide and the condensed intermediate was hydrolyzed followed by treatment with calcium ion source to provide the rosuvastatin calcium. The said process is having disadvantage of formation of high levels of unwanted Z isomer up to 5% along with required E isomer. Hence there is a need in the art for an improved process which able to control the formation of the unwanted isomer.
N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide and its use in the in the preparation of statin compounds (HMG-CoA reductase inhibitors) was also disclosed in PCT publication number WO 2008/044243. The said publication disclosed different processes for the preparation of the same.
Statin compounds such as rosuvastatin, pitavastatin, fluvastatin, atorvastatin, simvastatin and lovastatin are important drugs used for treatment of cholesterol reduction. Hence it is advantageous to have a novel and efficient process for the preparation of important intermediate like N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide, so that it can be used effectively in the preparation of statin compounds.
There is always need to improve the process efficiency for the preparation of important drugs. Hence the main objective of the present invention is to provide an improved process for the preparation of compound of formula-1 which controls the formation of unwanted isomer and also provides the novel crystalline forms of compound of formula-1a and its use. And also to provide novel and efficient process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide, which is more effective and easy to scale up to commercial level in a convenient and cost effective manner.